This comparative effectiveness research proposal aims to support a multicenter, prospective, randomized, NIH-defined phase III clinical trial to compare treatment protocols for decreased vision due to macular edema secondary to central retinal vein occlusion (CRVO) based on results of recent randomized trials. This application is an investigator-initiated project in response to Program Anouncement Number PAR-10-207. The trial is designed to assess whether bevacizumab is non-inferior to aflibercept (with the ability to test for superiority) for the treatment of decreased vision attributable to macular edem due to CRVO. The primary aim is to test for non-inferiority based on mean change from baseline in visual acuity letter score at Month 6 for eyes randomized to intravitreal bevacizumab every 4 weeks compared with eyes randomized to intravitreal aflibercept every 4 weeks using a non-inferiority margin of 5 letters. Secondary aims are to: compare the bevacizumab and the aflibercept groups in central retinal thickness at Month 6 and change between baseline and Month 6 as measured with spectral domain optical coherence tomography (SD-OCT); assess Month 13 visual acuity and SD-OCT outcomes associated with different dosing strategies after Month 6 in participants who respond well (defined per protocol) to treatment; assess Month 13 visual acuity and SD-OCT outcomes associated with alternative treatment strategies after Month 6 in participants who respond poorly (defined per protocol) to treatment; compare rates of neovascular complications of CRVO in the bevacizumab vs. aflibercept groups; add to our knowledge of the safety profile of these anti-vascular endothelial growth factor (anti-VEGF) medications in the setting of eyes with macular edema secondary to CRVO A total of 360 participants will be enrolled at approximately 80 clinical centers. Participants will be followed fr 13 months, with assessments including Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity letter score, SD-OCT, stereoscopic fundus photography and, at selected sites, widefield fluorescein angiography. Potential adverse events will be monitored with respect to frequency and severity.